Unfolded Protein Response and A Possible Treatment for CFS

[skwag]

Yeah, pretty much. I'm continuing with NAG and Choline/Inositol, which I started taking during my trial, and a lot of supplements I have been taking for years.

Currently trying out Miyarisan and soon to start b12 injections.

 

[mariovitali]

Yeah, pretty much. I'm continuing with NAG and Choline/Inositol, which I started taking during my trial, and a lot of supplements I have been taking for years.

Currently trying out Miyarisan and soon to start b12 injections.

OK, Good Luck!

 

[mariovitali]

@skwag

Your post got me interested more regarding Rituximab. So It works by destroying B-Cells. For this reason i entered B-Cells to the topics that i have on my software. Needless to say that i am amazed on how many Topics that i keep match with "B-Cells"


I will re-run the Association Analysis and report back

*********Topic : b-cell ***************
rituximab.csv : 28.18 %
b-cells.csv : 26.54 %
chop.csv : 14.98 %
ebv.csv : 12.35 %
cvid.csv : 9.18 %
hypogammaglobulynemia.csv : 9.05 %
xbp1.csv : 4.35 %
immune_response.csv : 2.27 %
pbmc.csv : 2.26 %
il_10.csv : 1.83 %
caspase_human.csv : 1.69 %
p53.csv : 1.45 %
histone_deacetylase.csv : 1.39 %
th1th2.csv : 1.19 %
cyp7b1.csv : 1.16 %
stat1.csv : 1.03 %
vcam-1.csv : 1.02 %
systemic_amyloidosis.csv : 0.97 %
phosphorylation.csv : 0.92 %
upr.csv : 0.89 %
floaters.csv : 0.88 %
glycoproteins.csv : 0.88 %
ubiquitination.csv : 0.88 %
atf4.csv : 0.82 %
glutaredoxin.csv : 0.81 %
biliary_cirrhosis.csv : 0.81 %
perk.csv : 0.80 %
er_stress.csv : 0.79 %
atf6.csv : 0.79 %
gpr78.csv : 0.79 %
5mthf.csv : 0.77 %
ire1.csv : 0.77 %
o-glcnacylation.csv : 0.75 %
nlinkedglycosylation.csv : 0.71 %
redox_homeostasis.csv : 0.71 %
o-glcnac.csv : 0.70 %
dexamethasone.csv : 0.69 %
daoa.csv : 0.68 %
mastocytosis.csv : 0.64 %
thioredoxin.csv : 0.58 %
pdhc.csv : 0.58 %
nad.csv : 0.57 %
amyloidosis.csv : 0.57 %
sirt3.csv : 0.55 %
sod2.csv : 0.55 %
nqo1.csv : 0.54 %
cyp1b1.csv : 0.53 %
redox_regulation.csv : 0.52 %
gnmt.csv : 0.51 %
inositol.csv : 0.50 %
mast_cell_activation.csv : 0.48 %
oxidative_protein_folding.csv : 0.47 %
heat_shock_protein.csv : 0.45 %
nr3c1.csv : 0.45 %
neuroinflammation.csv : 0.45 %
glutathione_stransferase.csv : 0.44 %
lactic_acidosis.csv : 0.43 %
glycosylation.csv : 0.43 %
glucocorticoid_receptor.csv : 0.43 %
chaperones.csv : 0.43 %
peroxiredoxin.csv : 0.42 %
gluten.csv : 0.41 %
d-limonene.csv : 0.41 %
prpc.csv : 0.41 %
sirt1.csv : 0.41 %
inflammatory_response.csv : 0.41 %
inducible_nos.csv : 0.40 %
hsp70.csv : 0.40 %
acetylation.csv : 0.39 %
gut.csv : 0.39 %
phosphatidylserine.csv : 0.38 %
mitochondrial_dysfunction.csv : 0.38 %
pyrogen.csv : 0.37 %
insp3.csv : 0.37 %
mcp-1.csv : 0.36 %
ros.csv : 0.36 %
hmgb1.csv : 0.34 %
nrf2.csv : 0.33 %
amyloid.csv : 0.33 %
adrenal_insufficiency.csv : 0.33 %
bdnf.csv : 0.33 %
curcumin.csv : 0.33 %
n-acetylglucosamine.csv : 0.32 %
glycolysis.csv : 0.31 %
resveratrol.csv : 0.31 %
nox4.csv : 0.31 %
crohns_disease.csv : 0.31 %
cfs.csv : 0.30 %
rar.csv : 0.30 %
acetylcholine.csv : 0.30 %
human_proteinuria.csv : 0.29 %
pdi.csv : 0.29 %
nac.csv : 0.29 %
urea_cycle.csv : 0.28 %
microglia.csv : 0.28 %
insulin_resistance.csv : 0.27 %
conjugation.csv : 0.27 %
cofactor.csv : 0.27 %
serca.csv : 0.27 %
csad.csv : 0.26 %
reactive_metabolites.csv : 0.26 %
mthfr.csv : 0.26 %
ngf.csv : 0.26 %
hepatocytes.csv : 0.26 %
sod3.csv : 0.26 %
disulfide_bonds.csv : 0.26 %
dim.csv : 0.26 %
liver_disease.csv : 0.26 %
phospholipid_human.csv : 0.25 %
hsc.csv : 0.25 %
fad.csv : 0.24 %
solute_carrier.csv : 0.24 %
sirt2.csv : 0.24 %
lithium_treatment.csv : 0.24 %
protease_inhibitor.csv : 0.23 %
reactive_intermediates.csv : 0.23 %
endothelial_nos.csv : 0.23 %
sinusitis.csv : 0.23 %
glutamine.csv : 0.23 %
glucose-6-phosphatase.csv : 0.23 %
butyrate.csv : 0.23 %
nadh_dehydrogenase.csv : 0.22 %
redox_potential.csv : 0.22 %
ptp1b.csv : 0.22 %
freet3.csv : 0.22 %
cholestasis.csv : 0.22 %
cyp1a1.csv : 0.22 %
flavoprotein.csv : 0.21 %
calcium_homeostasis.csv : 0.21 %
isotretinoin.csv : 0.21 %
misfolded_proteins.csv : 0.21 %
vitamin_d3.csv : 0.21 %
oxidative_stress_markers.csv : 0.20 %
detoxification.csv : 0.20 %
esr1.csv : 0.20 %
cox-2.csv : 0.20 %
ckd.csv : 0.20 %
pomc.csv : 0.20 %
udpglcnac.csv : 0.19 %
choline_deficiency.csv : 0.19 %
l-cysteine.csv : 0.19 %
astrocytes.csv : 0.19 %
neurite_outgrowth.csv : 0.19 %
nadph.csv : 0.19 %
nachr.csv : 0.19 %
sod1.csv : 0.18 %
caloric_restriction.csv : 0.18 %
hexosamine.csv : 0.18 %
biotin.csv : 0.18 %
oxidative_stress_protection.csv : 0.18 %
coenzymeq10.csv : 0.18 %
cortisol.csv : 0.18 %
cyp2e1.csv : 0.17 %
h2o2.csv : 0.17 %
ppp.csv : 0.17 %
gsh.csv : 0.17 %
lipoic_acid.csv : 0.17 %
sulfotransferase.csv : 0.16 %
gtp_cyclohydrolase.csv : 0.16 %
quinone_reductase.csv : 0.16 %
liver_injury.csv : 0.16 %
sarcosine.csv : 0.16 %
advanced_glycation_end.csv : 0.16 %
sulforaphane.csv : 0.16 %
sulfite_oxidase.csv : 0.16 %
microbiome_humans.csv : 0.16 %
glutamate.csv : 0.16 %
probiotics.csv : 0.15 %
tau.csv : 0.15 %
hepatotoxicity.csv : 0.15 %
adrenergic_receptor.csv : 0.14 %
testosterone_production.csv : 0.14 %
fmo3.csv : 0.13 %
l-arginine.csv : 0.13 %
hba1c.csv : 0.13 %
tbars.csv : 0.13 %
methionine.csv : 0.13 %
cyp1a2.csv : 0.13 %
catalase.csv : 0.13 %
adrenal_hyperplasia.csv : 0.13 %
hgh.csv : 0.12 %
l_tyrosine.csv : 0.12 %
cyp2d6.csv : 0.12 %
subclinicalhypo.csv : 0.12 %
rxr.csv : 0.12 %
trpv.csv : 0.12 %
omega3.csv : 0.12 %
glycerylphosphorylcholine.csv : 0.12 %
n-acetyltransferase.csv : 0.11 %
constipation.csv : 0.11 %
dolichol.csv : 0.11 %
choline.csv : 0.11 %
pyruvate_carboxylase.csv : 0.11 %
ggt.csv : 0.11 %
cortisol_levels.csv : 0.11 %
zinc_supplementation.csv : 0.11 %
xanthine_oxidase.csv : 0.11 %
p450.csv : 0.11 %
excitotoxicity.csv : 0.10 %
dht.csv : 0.10 %
ugt1a1.csv : 0.10 %
bilirubin.csv : 0.10 %
steatohepatitis.csv : 0.10 %
erad.csv : 0.10 %
dhea.csv : 0.10 %
exercise_intolerance.csv : 0.10 %
are.csv : 0.10 %
cimetidine.csv : 0.10 %
dihydroprogesterone.csv : 0.10 %
selenium.csv : 0.09 %
tetrahydrobiopterin.csv : 0.09 %
l_tryptophan.csv : 0.09 %
hydrogen_sulfide.csv : 0.09 %
phospholamban.csv : 0.09 %
phosphatidylcholine.csv : 0.09 %
hydroxysteroid_dehydrogenase.csv : 0.09 %
acetyl-coa.csv : 0.09 %
redox_cofactor.csv : 0.09 %
peroxynitrite.csv : 0.09 %
triiodothyronine_levels.csv : 0.08 %
hpa_axis.csv : 0.08 %
anhedonia.csv : 0.08 %
histamine.csv : 0.08 %
sulfation.csv : 0.08 %
p5p.csv : 0.08 %
uric_acid.csv : 0.08 %
nafld.csv : 0.08 %
pxr.csv : 0.08 %
acetyl_coa_carboxylase.csv : 0.08 %
nmda.csv : 0.07 %
isoprostane.csv : 0.07 %
p450oxidoreductase.csv : 0.07 %
cannabidiol.csv : 0.07 %
irritable_bowel.csv : 0.07 %
beta-alanine.csv : 0.07 %
monosodium_glutamate.csv : 0.07 %
uti.csv : 0.07 %
hmgcoa.csv : 0.07 %
oxidation.csv : 0.07 %
kainate.csv : 0.07 %
riboflavin.csv : 0.06 %
gaba_human.csv : 0.06 %
iron_deficiency.csv : 0.06 %
creatine_supplementation.csv : 0.06 %
angiotensin_human.csv : 0.06 %
l_carnitine.csv : 0.06 %
d_serine.csv : 0.06 %
human_semen.csv : 0.06 %
hypobaric_hypoxia.csv : 0.06 %
ginkgo.csv : 0.06 %
ampa.csv : 0.06 %
nitration.csv : 0.05 %
molybdenum.csv : 0.05 %
neuronal_nos.csv : 0.05 %
vitamin_k.csv : 0.05 %
ed.csv : 0.05 %
liver_regeneration.csv : 0.05 %
sulfur.csv : 0.05 %
5alphareductase.csv : 0.05 %
enterohepatic_circulation.csv : 0.05 %
cyp3a4.csv : 0.05 %
norepinephrine.csv : 0.05 %
fluoroquinolone.csv : 0.05 %
urolithiasis.csv : 0.05 %
serotonin_levels.csv : 0.05 %
pregnenolone.csv : 0.04 %
asymmetric_dimethylarginine.csv : 0.04 %
sshl.csv : 0.04 %
dopamine.csv : 0.04 %
finasteride.csv : 0.04 %
dysautonomia.csv : 0.04 %
monoamine_oxidase.csv : 0.04 %
5-htp.csv : 0.04 %
niacin.csv : 0.04 %
l-dopa.csv : 0.04 %
hyperammonemia.csv : 0.03 %
sleep_apnea.csv : 0.03 %
fmn.csv : 0.03 %
taurine.csv : 0.03 %
atrial_fibrillation.csv : 0.03 %
panic_disorder.csv : 0.03 %
ciprofloxacin.csv : 0.03 %
autism.csv : 0.03 %
selenium_deficiency.csv : 0.03 %
hydrolysis.csv : 0.03 %
steroidogenesis_human.csv : 0.02 %
magnesium_deficiency.csv : 0.02 %
3betahsd.csv : 0.02 %
insomnia.csv : 0.02 %
lpa.csv : 0.02 %
glucuronidation.csv : 0.02 %
tinnitus.csv : 0.02 %
thermoregulation.csv : 0.02 %
bradycardia.csv : 0.02 %
5-ht2.csv : 0.02 %
limbic_system.csv : 0.02 %
peristalsis.csv : 0.02 %
udpgluc.csv : 0.02 %
orthostatic_intolerance.csv : 0.01 %
thiamine.csv : 0.01 %
baroreceptor.csv : 0.01 %
oxalates.csv : 0.01 %
bile_acid.csv : 0.01 %
social_anxiety.csv : 0.01 %
adhd.csv : 0.00 %
artichoke.csv : 0.00 %
cyp7a1.csv : 0.00 %
car.csv : 0.00 %
vitamin_b6.csv : 0.00 %
akr1d1.csv : 0.00 %
star.csv : 0.00 %
p450scc.csv : 0.00 %
pantothenic_acid.csv : 0.00 %
cysteine_desulfurase.csv : 0.00 %
ae2.csv : 0.00 %
ndufs7.csv : 0.00 %
dpagt1.csv : 0.00 %
phenylketonuria.csv : 0.00 %
pqq.csv : 0.00 %
mucuna.csv : 0.00 %
fads1.csv : 0.00 %
allopregnanolone.csv : 0.00 %
fxr.csv : 0.00 %
sult2a1.csv : 0.00 %
3methylcrotonyl_coa_carboxylase.csv : 0.00 %
cyp27a1.csv : 0.00 %
pgc1.csv : 0.00 %
intestinal_motility.csv : 0.00 %
d_aminoacid_oxidase.csv : 0.00 %
cerebrovascular_amyloidosis.csv : 0.00 %
hnmt.csv : 0.00 %
benfotiamine.csv : 0.00 %
cyp8b1.csv : 0.00 %
ugt1a9.csv : 0.00 %
scfa.csv : 0.00 %
srd5a3.csv : 0.00 %
tudca.csv : 0.00 %
potassium_levels.csv : 0.00 %
propionyl_coa_carboxylase.csv : 0.00 %
rls.csv : 0.00 %
ero1.csv : 0.00 %
gilberts.csv : 0.00 %
tocotrienol.csv : 0.00 %
resistant_starch.csv : 0.00 %
fads2.csv : 0.00 %
osmolytes.csv : 0.00 %
pantethine.csv : 0.00 %
tmao.csv : 0.00 %

 

[Tunguska]

@Tunguska

First things first :


1) The fact that i don't have a sufficient amount of cases (=their DNA Data) of People that do not have CFS/PFS/Accutane/..//.. Syndromes is a serious limitation.

2) Even if that Data existed, there are so many other factors (Gender, Age, Environment, etc etc) that further make things even more difficult.

3) To make things even worse, there are so many genes involved with the Topics that are being discussed in this Thread.

A couple of things that i don't know about you (if possible please send them as a PM) :

1) How did you get CFS?
2) When you say "i have multiple" what do you mean? You have CFS *and* Post-Lyme Disease *and* PFS ...??
3) How are your P450 CYPs according to Nutrahacker?

Some notes regarding the Alleles you sent me :

1. I would like to first point your attention to your ATF6 Alleles: One homozygous to ATF6, 1 hetero to ATF6. Then you have 1 homozygous to Cholestasis, several to NOS2, Several to Sulfation, several to NR3C1. Finally homozygous to NFE2L2 aka NRF2. Did you see NRF2 and ATF6 towards the top of the list on the snapshot of the Data Mining tool ?

2. Of course this (= the alleles) may not mean a thing. There may be so many others here that do not have -say- ATF6 alleles and NRF2 alleles and yet they have CFS. What i am trying to say is : Try to see the Big picture. There are several holes in the Redox system : Choline, Methylation, Sulfation, Glucuronidation, ER Stress Response, P450 CYPs activity, Redox co-factors, etc, etc. ..and ALL of these paint the Big Picture.

Regarding Choline i do not know what is best unfortunately.

@Tunguska I am willing to work with you. So if you want to give this a chance let's go for it. Then you will be able to say exactly what happened to all members of the Forum.


Let me know what you think.

Thank you, but I don't think there's a lot you can do for me at this stage. The suggestion to try TUDCA was helpful enough. Your supplement table is interesting as well, but I'm already well acquainted with all those supplements and tried a lot of variations so the specifics of combinations (stages) it suggests have potential to help but do not add enough information for myself to use yet. My existing regimen covers much of it.

Yes I have CFS/whatever, accutane changes and fluoroquinolone toxicity, to name a few. Poor liver enzyme SNPs was the overall picture given by promethease. But even that was no longer useful information by then. ATF6 even if meaningful would only add a little to that. I already found out the most important part of the big picture the hardest way possible [other parts I've ruled out experimentally or already cover preventatively by regimen]. Individual SNPs I have enough reasons not to rely on [to select treatment].

Unusual sensitivity of blood flow to acetylcholine (a neurotransmitter)

I experience this indirectly. I need choline precursors to maintain mental function but they noticeably affect blood flow negatively and constriction in the day. It's a real hindrance.

 

[mariovitali]

@Tunguska

My suggestion : Try anything you can to thoroughly check and support your Liver. Anytime you want PM me.


@skwag

As discussed, i am trying to understand the connection between B-Cells and the fact that they matched a lot of the PubMed topics i have under consideration :


Recall that the tool searches in different "perspectives" ( ie being either General or Specific )


The runs for B-Cells :

We see that Rituximab is there but also Immunoglobulins such as IgM and IgE.


Next run :

So there appears to be a connection between B-Cells, Heat-shock Proteins (discussed in this Thread), N-Linked Glycosylation (discussed in this Thread, First post).

So how come N-Linkedglycosylation was found to be associated with Rituximab? From the Wikipedia for N-Linked Glycosylation

Many “blockbuster” therapeutic proteins in the market are antibodies, which are N-linked glycoproteins. For example, Etanercept, Infliximab and Rituximab are N-glycosylated therapeutic proteins.



The importance of N-linked glycosylation is becoming increasingly evident in the field of pharmaceuticals.

Link : https://en.wikipedia.org/wiki/N-linked_glycosylation


Now a run about Rituximab itself :

Notice that a lot of (*itis) but also uti (=urinary tract infection) exist around. Apart from this we see something called ERAD :

Endoplasmic-reticulum-associated protein degradation (ERAD) designates a cellular pathway which targets misfolded proteins of the endoplasmic reticulum for ubiquitination and subsequent degradation by a protein-degrading complex, called the proteasome.

I then search for a connection between HSPs, B-Cells and Endoplasmic Reticulum :

Endoplasmic reticulum HSP90b1 (gp96, grp94) optimizes B-cell function via chaperoning integrin and TLR but not immunoglobulin.
Liu B1, Li Z.
Author information

• 1Department of Immunology, Center for Immunotherapy of Cancer and Infectious Diseases, Neag Comprehensive Cancer Center, University of Connecticut School of Medicine, Farmington, CT 06030-1601, USA.

Abstract
Endoplasmic reticulum (ER) unfolded protein response (UPR) plays pivotal roles in both early B-cell development and plasma cell differentiation. As a major ER chaperone to mediate the UPR and a master chaperone for Toll-like receptors (TLRs), HSP90b1 (grp94, gp96) has long been implicated to facilitate the assembly of immunoglobulin. We hereby critically and comprehensively examine the roles of HSP90b1 in B-cell biology in vivo using B-cell-specific HSP90b1-null mice. We found that knockout B cells developed normally. There were no apparent problems with plasma cell differentiation, Ig assembly, class-switching, and Ig production. Strikingly, although both mutant conventional and innatelike B cells failed to compartmentalize properly due to loss of select but not all integrins, HSP90b1 was required for neither germinal center formation nor memory antibody responses in vivo. The only significant defect associated with HSP90b1 ablation in B cells was an attenuated antibody production in the context of TLR stimulation. Thus, our study has resolved the long-standing question regarding HSP90b1 in B-cell biology: HSP90b1 optimizes the function of B cells by chaperoning TLRs and integrins but not immunoglobulin. This study also has important implications in resolving the controversial roles of TLR in B-cell biology.

Remember that Rituximab works by destroying B-Cells.

At another run, the tool has found a possible association association between TLR and B-Cells

(Note 'tlr' in the results)

[

Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors usually expressed insentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have breached physical barriers such as the skin or intestinal tractmucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8,TLR9, TLR10, TLR11, TLR12, and TLR13, though the latter three are not found in humans.

More about the connection between B-Cells and the ER :

It is interesting to note that PrxIV is upregulated dramatically in line with ER oxidoreductases as the ER expands during B-cell differentiation to ensure efficient synthesis of immunoglobulins (van Anken et al., 2003). However, PrxIV does not seem to be induced during the UPR (Tavender et al., 2008). It could be that during differentiation, levels of PrxIV need to increase to accommodate the increased load of disulphide formation, but during UPR, levels need to remain constant to allow signalling of oxidative stress. Clearly, more work is needed to clarify this point.

Reference : Signaling Pathways in Liver Disease (2010)

 

[skwag]

Hi Mario,

One reason for all the matches you initially found may be that your topics naturally have a lot overlap with "primary biliary cirrhosis (PBC)," as we've seen in older posts. As PBC is a known autoimmune condition, there has been some studies using Rituximab to treat it. For example, here.

Unfortunately, as of now I can't claim to understand the other links you may have uncovered.

 

[mariovitali]

@skwag

Yes i have seen that regarding PBC as well in other runs.

I did not make any comments for a reason. I just wished to identify that B-Cells, N-Linked Glycosylation and Endoplasmic Reticulum appear to be connected. I do not have the proper knowledge to understand more or to make any further connections on the subjects i posted.

 

[Violeta]

http://www.ncbi.nlm.nih.gov/pubmed/7729416

Epstein-Barr virus efficiently immortalizes human B cells without neutralizing the function of p53

http://www.ncbi.nlm.nih.gov/pubmed/15890964

Heat shock protein 90 expression in Epstein-Barr virus-infected B cells promotes gammadelta T-cell proliferation in vitro.

 

[mariovitali]

So , here is why i ended up with problems (i think)


5α-Reductase type 1 deficiency or inhibition predisposes to insulin resistance, hepatic steatosis, and liver fibrosis in rodents.
Livingstone DE1, Barat P2, Di Rollo EM2, Rees GA2, Weldin BA2, Rog-Zielinska EA2, MacFarlane DP2, Walker BR2, Andrew R2.
Author information

Abstract
5α-Reductase type 1 (5αR1) catalyses A-ring reduction of androgens and glucocorticoids in liver, potentially influencing hepatic manifestations of the metabolic syndrome. Male mice, homozygous for a disrupted 5αR1 allele (5αR1 knockout [KO] mice), were studied after metabolic (high-fat diet) and fibrotic (carbon tetrachloride [CCl4]) challenge. The effect of the 5α-reductase inhibitor finasteride on metabolism was investigated in male obese Zucker rats. While eating a high-fat diet, male 5αR1-KO mice demonstrated greater mean weight gain (21.6 ± 1.4 vs 16.2 ± 2.4 g), hyperinsulinemia (insulin area under the curve during glucose tolerance test 609 ± 103 vs. 313 ± 66 ng ⋅ mL(-1) ⋅ min), and hepatic steatosis (liver triglycerides 136.1 ± 17.0 vs. 89.3 ± 12.1 μmol ⋅ g(-1)). mRNA transcript profiles in liver were consistent with decreased fatty acid β-oxidation and increased triglyceride storage. 5αR1-KO male mice were more susceptible to fibrosis after CCl4 administration (37% increase in collagen staining). The nonselective 5α-reductase inhibitor finasteride induced hyperinsulinemia and hepatic steatosis (10.6 ± 1.2 vs. 7.0 ± 1.0 μmol ⋅ g(-1)) in obese male Zucker rats, both intact and castrated. 5αR1 deficiency induces insulin resistance and hepatic steatosis, consistent with the intrahepatic accumulation of glucocorticoids, and predisposes to hepatic fibrosis. Hepatic steatosis is independent of androgens in rats. Variations in 5αR1 activity in obesity and with nonselective 5α-reductase inhibition in men with prostate disease may have important consequences for the onset and progression of metabolic liver disease.

 

[Violeta]

Does that give you any extra clues about what might help? Maybe berberine?

 

[Violeta]

Maybe looking at AMPK will provide some insight?

http://selfhacked.com/2014/11/21/natural-ampk-activators/

 

[mariovitali]

@Violeta

I do not see how the things you are discussing are connected with 5-Alpha Reductase unfortunately

 

[ahmo]

@mariovitali I was just w/ my GP, talked about UDCA, but left w/o an rx, not because of him, but due to my ambivalence. My impression is that it hasn't proved to be a huge benefit, I can only recall now someone saying they'd tried and then quit it. Do you still think it's very important?

Also, I looked at inosine. It's described as antioxidant, anti-peroxynitrite. Any opinions about it?

And 3rd query, re B12. I'm not sure this is the right place, will be creating a new thread. I've reached a stable, very tolerable state, with almost no symptoms or pain. I've been considering injecting B12, which is very expensive. But I'm unclear whether this alone can transform my life, from doing very little activity to being able to tolerate more, better cognition. And I'm unclear whether this would mean I then must increase folate, which has stressed my adrenals in the past. thx.

 

[Violeta]

@Violeta

I do not see how the things you are discussing are connected with 5-Alpha Reductase unfortunately

With respect to berberine, "While berberine extract can help to normalize 5-alpha reductase, it also appears to have a major effect on your weight, cholesterol, blood pressure, insulin resistance, and hormones, according to a study from Shanxi Medical University in China."

 

[Violeta]

@Violeta

I do not see how the things you are discussing are connected with 5-Alpha Reductase unfortunately

With respect to AMPK:

Impaired glucose tolerance and insulin resistance are associated with increased adipose 11beta-hydroxysteroid dehydrogenase type 1 expression and elevated hepatic 5alpha-reductase activity.

In addition to glucose transport, lipid and protein synthesis, and fuel metabolism, AMPK regulates a wide array of other physiological events, including cellular growth and proliferation, mitochondrial function and biogenesis, and factors that have been linked to insulin resistance (IR), including inflammation, oxidative and ER stress, and autophagy

 

[mariovitali]

@ahmo

Can you send over the PDF with the Risk Alleles that you have? Could you also send over your Nutrahacker report regarding your P450 CYPs?

Regarding UDCA : TUDCA is a much better option as it is found to be much more "ER Ameliorating" from UDCA Alone. TUDCA on its own may not be doing many things in case you have several other "Redox holes" (my theory).

Again as i have said here previously i am willing to work with you under a Doctor's supervision of course and then you can post your experience if you did/didn't see any difference.

Regarding inosine : I will put it in my software and i will let you know. Regarding B12 i am probably not the right person as i do not know many things about it.


@Violeta

Thank you for all the info you provided They seem to be very interesting indeed.

 

[ahmo]

Can you send over the PDF with the Risk Alleles that you have? Could you also send over your Nutrahacker report regarding your P450 CYPs?

I don't have a Nutrahacker report. Risk alleles: genetic genie results?

 

[mariovitali]

I don't have a Nutrahacker report. Risk alleles: genetic genie results?

Ah Yes, Genetic genie's "Detox profile" lists several P450 CYPs so this will do. Apart from this, please send also the results regarding your RIsk Alleles shown on the PDF (NQO1, GCH1,PDILT,ATF6, etc)

 

[mariovitali]

Dear All,


I am attaching a file which is the basis for the Analysis that i am performing. It may prove useful in case that you are researching any subject possibly relevant to CFS. To generate this file it takes around 11 hours and the it consists of a total of 169790 lines.

FYI @ahmo : The latest addition is "inosine". As an example, if you are interested in "inosine", you search for that entry and then see which Topics are more commonly found along with inosine. In this case we have :


xanthine_oxidase.csv : 1.32 %
uric_acid.csv : 1.18 %
nad.csv : 0.88 %
monosodium_glutamate.csv : 0.78 %
ppp.csv : 0.63 %
benfotiamine.csv : 0.60 %
tmao.csv : 0.49 %

where ppp = Pentose Phosphate Pathway, tmao = Trimethylamine N-Oxide


So we see that "inosine" appears to be associated with Xanthine Oxidase. We search for inosine and xanthine oxidase in Google or Pubmed and we end up with this :


http://www.ncbi.nlm.nih.gov/pubmed/23091148

 

[Violeta]

I read yesterday that berberine works through Phase II glucuronidation, I should have bookmarked the link.

I just looked up glucuronidation and found this, if it's of interest to anyone.

Glucuronidation, more correctly glucuronosylation, is the addition of glucuronic acid to a substrate. Glucuronidation is often involved in xenobiotic metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids,glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds.[1